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Fig. 1 | Journal of Experimental & Clinical Cancer Research

Fig. 1

From: Relationship between epithelial-to-mesenchymal transition and the inflammatory microenvironment of hepatocellular carcinoma

Fig. 1

Tumor-associated macrophages and epithelial-to-mesenchymal transition in hepatocellular carcinoma. TNFα binds to the receptor TNFR (mainly TNFR1) to phosphorylate PKD2, which then forms a complex with PI3K. This complex stabilizes the high expression of β-catenin via the PI3K/AKT/GSK-3β pathway, upregulates Snail and Twist transcription, and participates in the process of epithelial-to-mesenchymal transition (EMT) to promote tumor invasion and metastasis. IL-8 secreted by TAMs participates in the EMT via the JAK2/STAT3/Snail pathway. It also activates FOXC1 via PI3K/AKT HIF-1α, leading to transactivation of CXC chemokine receptor (CXCR) and CC chemokine ligand 2 (CCL2), otherwise, neurotensin (NTS) and IL-8 are also activated abnormally, leading to upregulated expression of VEGF and MMP9 via the NTS/IL-8 pathway. IL-6 induces EMT by binding to the IL-6R receptor to induce STAT3 phosphorylation via the JAK/STAT3 pathway, leading to downregulated E-cadherin expression and upregulated vimentin expression. This interaction can also induce upregulation of the expression of Snail, ZEB1, ZEB2, Twist and other transcription factors to promote tumor metastasis. TGFβ secreted by TAMs modulates the expression of EMT-related genes at the epigenetic level via the classic TGF-β/TGF-β R/Smad signaling pathway. It also acts on Snail, Slug and other transcription factors via the RhoA/Cdc42, JKN/p38, Erk1/2 and PI3K/Akt pathways. EGF binds to hepatoma cell epidermal growth factor receptor (EGFR), activating downstream ERK/PI3K/AKT, ras/raf/MEK/MAPK, NF-κB and other pathways

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